Thioxanthene derivatives of pharmacological interest: 1,2,4-Trichloro and 2,4,5,6-tetrachloro derivatives of 9-(3-dimethylaminopropylidene)thioxanthene

1984 ◽  
Vol 49 (10) ◽  
pp. 2295-2308 ◽  
Author(s):  
Václav Bártl ◽  
Vojtěch Kmoníček ◽  
Zdeněk Šedivý ◽  
Emil Svátek ◽  
Jiří Protiva ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Amino Alcohols ◽  
Gram Positive ◽  
Pharmacological Interest ◽  
Acid Catalyzed ◽  
Cns Effects ◽  
Derivatives Of ◽  
Iodobenzoic Acid

Reactions of 2,4,5-trichlorothiophenol (II) with 2-iodobenzoic acid and 2,3-dichlorothiopheno with 3,5-dichloro-2-iodobenzoic acid gave the acids III and IX which were cyclized to thioxanthones VI and XV. Reactions of these ketones with 3-dimethylaminopropylmagnesium chloride afforded the amino alcohols VII and XVI which were transformed by the acid catalyzed dehydration to the title compounds I and VIII. 2-Chloro-9-[1-(2-hydroxyethyl)-4-piperidylidene]thioxanthene (XVII) was obtained by a modified synthesis. Compound I is inactive in the line of the CNS effects but it has high inhibitory activity in the in vitro tests towards gram-positive microorganisms. Compound XVII has properties of a mild tranquillizer.

Synthesis and Biological Evaluation of Acetylcholinesterase Inhibitor Macakurzin C and Its Derivatives

Synlett ◽  
2015 ◽  
Vol 26 (08) ◽  
pp. 1131-1134 ◽  
Author(s):  
Hyoungsu Kim ◽  
Seung-Hoon Baek ◽  
Hongjun Jang
Keyword(s):  
Inhibitory Activity ◽  
Acetylcholinesterase Inhibitor ◽  
Biological Evaluation ◽  
Hydroxyl Groups ◽  
Structural Requirements ◽  
Ache Inhibitory Activity ◽  
Synthesis And Biological Evaluation ◽  
Derivatives Of

The derivatives of macakurzin C containing a modified D ring and protected C(3)/C(5)-hydroxyl groups were synthesized and their in vitro AChE inhibitory activity and neurotoxicity were evaluated to identify the structural requirements for the activities. The results indicated that C(3)-benzyl-protected derivative has a more potent AChE inhibitory activity (IC50, 2.6 μM) and a less neurotoxicity (GI50, >100 μM) than synthetic macakurzin C (IC50, 9.1 μM; GI50, 16.6 μM).

scholarly journals Synthesis and Antimicrobial Evaluations of Sulfur Inserted Fluoro-Benzimidazoles

2021 ◽  
Vol 33 (7) ◽  
pp. 1525-1529
Author(s):  
Parmesh Kumar Dwivedi ◽  
Devdutt Chaturvedi
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Strains ◽  
Substituted Anilines ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
New Compounds ◽  
Derivatives Of ◽  
Multiple Step

A new series of fluorinated sulfur inserted benzimidazole analogues Za-i were synthesized and characterized. The new compounds were screened for their antimicrobial and antioxidant potential. The synthesized compounds were obtained by multiple step synthesis, initiating from the synthesis of 5-(difluoromethoxy)-1H-benzimidazole-2-thiol X. The compounds Ya-i prepared by reacting differently substituted anilines with chloroacetylchloride and triethylamine in DMF. Finally, the compound X was reacted with different derivatives of 2-chloro-N-phenylacetamide resulting in formation of titled compounds Za-i. The synthesized compounds (Za-Zi) were characterized by spectral analysis viz.1H & 13C NMR, mass spectra, elemental analysis and IR. The in vitro antimicrobial potential against Gram-positive (S. aureus and E. faecalis) and Gram-negative bacterial (E. coli and P.aeruginosa) strains as well as fungi (A. niger and C. albicans) was recorded for the obtained compounds. Some of the compounds exhibited encouraging results (in MIC) against Gram-positive and Gram-negative bacterial strains. These studies thus suggest that the designed sulfur inserted fluoro-benzimidazoles scaffold may serve as new promising template for further amplification as antimicrobial agents.

Semisynthetic cephalosporins. The synthesis of 7-(heteroarylacetamido)-3-acetoxycephalosporanic acids

1985 ◽  
Vol 50 (2) ◽  
pp. 482-491 ◽  
Author(s):  
Ľubomír Janda ◽  
Zdeno Votický ◽  
Ján Šipoš ◽  
Marta Múčková
Keyword(s):  
Gram Positive ◽  
Sodium Salts ◽  
Gram Negative ◽  
Derivatives Of ◽  
Better Than

7-(5-(5-Aryl-2-furyl)-1- and -2-tetrazolylacetamido)cephalosporanic acids and their sodium salts were prepared by N-acylation of 7-aminocephalosporanic acid with derivatives of 5-(5-aryl-2-furyl)-1- and -2-tetrazolylacetic acids. The final products tested in vitro on the Gram-positive and Gram-negative strains of microorganisms showed an activity comparable or better than that of reference substances.

Synthesis and In Vitro Biological Activity Evaluation of Novel Imidazo [2,1-B][1,3,4] Thiadiazole as Anti-Alzheimer Agents

2020 ◽  
Vol 17 (5) ◽  
pp. 610-617
Author(s):  
Sara Azimi ◽  
Omidreza Firuzi ◽  
Aida Iraji ◽  
Afsaneh Zonouzi ◽  
Mahsima Khoshneviszadeh ◽  
...  
Keyword(s):  
Biological Activity ◽  
Inhibitory Activity ◽  
Phenyl Ring ◽  
Activity Evaluation ◽  
Butyryl Cholinesterase ◽  
Thiadiazole Derivatives ◽  
Derivatives Of

Background: Considering that AD is multifactorial in nature, novel series of imidazo [2,1-b][1,3,4] thiadiazole derivatives were designed to address the basic factors responsible for the disease. <p> Methods: These compounds were investigated as inhibitors of beta-site APP cleaving enzyme 1, acetylcholinesterase and butyryl cholinesterase. <p> Results: The BACE1 inhibitory results indicated that nitro phenyl substituted derivatives of imidazo [2,1-b][1,3,4] thiadiazole scaffold (R2 = m-NO2) demonstrated superior BACE1 inhibitory activity compared to other substituted moieties. In the BuChE assay, compounds 4h and 4l carrying meta NO2 at R2 of phenyl ring turned out to be potent inhibitors. <p> Conclusion: In conclusion, these novel synthesized derivatives seem to be promising anti-Alzheimer agents.

SEMI-SYNTHESIS AND EVALUATION OF HESPERETIN DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS7

2018 ◽  
Vol 8 (4) ◽  
pp. 7-12
Author(s):  
Huan Tran The ◽  
Dao Tran Thanh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Key Words ◽  
Inhibitory Activity ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Ic50 Value ◽  
Ellman’S Method ◽  
Further Development ◽  
Derivatives Of

Background: Inhibition of acetylcholinesterase are regarded as one of promising approach to treat Alzheimer’s disease. Hesperetin is a potential flavonoid for further development in this direction. Objectives: Semi-synthesized and assayed for hesperetin derivatives’s acetylcholinesterase inhibitory activity in vitro. Materials and methods: Ester and ether derivatives of hesperetin were semi-synthesized. The semi-synthesis compounds were tested for acetylcholinesterase inhibitory activity in vitro according to the Ellman’s method. Results: Hesperetin is obtained by hydrolysing hesperidin. Then, two ester and two ether derivatives were semi-synthesized from hesperetin. The results showed that some of the semi-synthesis hesperetin derivatives displayed stronger acetylcholinesterase inhibitory activity than hesperetin. Among them, derivative 1 has the best activity with an IC50 value of 43.50 μM. Conclusions: Four hesperetin derivatives were semi-synthesized and investigated their acetylcholinesterase inhibitory activity, some of which showed improvement in activity. Key words: Hesperetin, semi-synthesis, inhibit, enzyme, acetylcholinesterase

ENZYME INHIBITION BY DERIVATIVES OF PHENOTHIAZINE AND OF SULPHANILAMIDE

1940 ◽  
Vol 18b (11) ◽  
pp. 345-350 ◽  
Author(s):  
H. B. Collier
Keyword(s):  
Cytochrome C ◽  
Cytochrome Oxidase ◽  
Enzyme Inhibition ◽  
Ascaris Lumbricoides ◽  
Inhibitory Activity ◽  
Spectroscopic Observation ◽  
Hydroxyl Group ◽  
Bactericidal Action ◽  
Derivatives Of

Mammalian catalase and cytochrome oxidase are strongly inhibited by the hydroxy derivatives of phenothiazine and by p-hydroxylaminobenzenesulphonamide. Phenothiazine, sulphanilamide, and sulphapyridine have little or no effect. Cytochrome-c is irreversibly reduced by the hydroxy-sulphanilamide, as indicated by spectroscopic observation. The inhibitory activity apparently depends on the presence of the hydroxyl group. The relation of these findings to the vermicidal and bactericidal action of the compounds is discussed.Phenothiazine and thionol have no effect on Ascaris lumbricoides in vitro.

scholarly journals Design and synthesis of novel pyrazole-benzofuran hybrids: in vitro α-glucosidase inhibitory activity, kinetic and molecular modeling study

2021 ◽  
Author(s):  
Fateme Azimi ◽  
Homa Azizian ◽  
Mohammad Najafi ◽  
Ghadamali khodarahmi ◽  
Motahareh hassanzadeh ◽  
...  
Keyword(s):  
Active Site ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Back Side ◽  
Binding Interaction ◽  
Dynamic Simulations ◽  
Standard Drug ◽  
Design And Synthesis ◽  
Derivatives Of

Abstract In this work, new derivatives of biphenyl pyrazole-benzofuran hybrids designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 µM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with Ki = 38 µM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme.

scholarly journals Study of the Anti-Proliferative Activity of 5-Substituted 4,7-Dimethoxy-1,3-Benzodioxole Derivatives of SY-1 fromAntrodia camphorataon Human COLO 205 Colon Cancer Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hsiu-Man Lien ◽  
Po-Tsun Kuo ◽  
Chao-Lu Huang ◽  
Jung-Yie Kao ◽  
Ho Lin ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Carcinoma Cells ◽  
Flow Cytometry Analysis ◽  
Antrodia Camphorata ◽  
Cycle Arrest ◽  
Normal Human ◽  
G1 Cell Cycle Arrest ◽  
Derivatives Of ◽  
Potent Inhibitory Activity

A set of 10 4,7-dimethoxy-1,3-benzodioxole derivatives based on a lead compound previously discovered by our group, SY-1, which was isolated fromAntrodia camphorata, were evaluated for theirin vitroinhibitory activity on human colorectal carcinoma cells (COLO 205). Structure-activity relationship studies of the 10 compounds indicated the importance of the chain length of the alkyl group at the 5-position, and the 2-propenyl substituent named “apiole” exhibited the most potent inhibitory activity. In the present study, we demonstrate that the SY-1 analogue “apiole” decreased the proliferation of COLO 205 cells, but not that of normal human colonic epithelial cells (FHC). The G0/G1 cell cycle arrest induced by apiole (75–225 μM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, apiole (>150 μM) treatment significantly increased the levels of cleaved caspases 3, 8, 9 and bax/bcl-2 ratio and induced ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. These findings suggest that apiole can suppress COLO 205 cell growth; however, the detailed mechanisms of these processes require further investigation.

scholarly journals In Vitro Activities of Novel Oxapenems, Alone and in Combination with Ceftazidime, against Gram-Positive and Gram-Negative Organisms

2003 ◽  
Vol 47 (8) ◽  
pp. 2615-2618 ◽  
Author(s):  
Conor E. Jamieson ◽  
Peter A. Lambert ◽  
Iain N. Simpson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clavulanic Acid ◽  
Inhibitory Activity ◽  
Gram Positive ◽  
Active Compounds ◽  
Gram Negative ◽  
Class A ◽  
Class C ◽  
Gram Negative Organisms

ABSTRACT Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their β-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum β-lactamase enzymes (ESBLs). The oxapenems were potent β-lactamase inhibitors. Activity varied within the group, with AM-113 and AM-114 proving to be the most active compounds. The 50% inhibitory concentrations for these agents were up to 100,000-fold lower than that of clavulanic acid against class C and D enzymes. As a group, the oxapenems were more potent than clavulanic acid against enzymes from all classes. The ability of these compounds to protect ceftazidime from hydrolysis by β-lactamase-producing strains was evaluated by MIC tests that combined ceftazidime and each oxapenem in a 1:1 or 2:1 ratio. The oxapenems markedly reduced the MICs for ceftazidime against class C hyperproducing strains and strains producing TEM- and SHV-derived ESBLs. There was little difference between the activity of 1:1 and 2:1 combinations of ceftazidime and oxapenem. The oxapenems failed to enhance the activity of ceftazidime against derepressed AmpC-producing Pseudomonas aeruginosa strains.

Potential metabolites of the neuroleptic agent chlorprothixene; synthesis and pharmacology of the 3-, 4-, 6- and 7-hydroxy and methoxy derivatives of 2-chloro-9-(3-dimethylaminopropylidene)-thioxanthenes

1980 ◽  
Vol 45 (11) ◽  
pp. 3166-3181 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Jílek ◽  
Jiří Körbl ◽  
Fedir Jančik ◽  
Emil Svátek ◽  
...  
Keyword(s):  
Ir Spectra ◽  
Polyphosphoric Acid ◽  
Amino Alcohols ◽  
Geometric Isomers ◽  
Pyridine Hydrochloride ◽  
Neuroleptic Agent ◽  
Acid Catalyzed ◽  
Boron Tribromide ◽  
Derivatives Of ◽  
Central Depressant

Cyclization of the acids IV-VII with sulfuric or polyphosphoric acid resulted in the thioxanthones VIIIa-d which were treated with 3-dimethylaminopropylmagnesium chloride and gave the amino alcohols Xa-d. Their acid catalyzed dehydrations afforded the methoxy derivatives of chlorprothixene IIIa-d, mostly in form of mixtures of geometric isomers. Whereas the results of attempts to demethylate these products with boron tribromide gave mostly unsatisfactory results, the demethylation with pyridine hydrochloride at 190-200 °C was successful; alcohols X were the most suitable starting materials. In this manner, the hydroxy derivatives of chloroprothixene IIa-d were obtained, mostly as pure geometric isomers. The configuration was assigned on the basis of their IR spectra. Z-Isomers are potential metabolites of the neuroleptic agent chlorprothixene (I). Compounds II and III are little toxic, have low central depressant activity and are inactive cataleptically.

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